The Effect and Mechanism of TLR9/KLF4 in FFA-Induced Adipocyte Inflammation

Abstract

Objective Current research has reported that obesity is a chronic inflammatory state, which is closely related with excessive accumulation of free fatty acid, while the specific mechanism that high level of FFA causes inflammation is not very clear. Thus, our research intended to observe the high FFA effects on TLR9/KLF4 expression and the downstream inflammatory factors, to explore the mechanism of inflammatory response suppressed by TLR9/KLF4. Methods qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of TLR9, KLF4, and key inflammation-related factors. ELISA was used to detect the release level of inflammatory cytokines. The triglyceride (TG) and glucose (GLU) testing cassettes were used to detect the TG and GLU levels in culture medium. Results In the omental tissue of obese individuals (OB), we found that TLR9, KLF4, mRNA, and the protein expression levels were lower than those of the normal weight control (NC) group. Similarly, in the omental tissue of high-fat diet (HFD) rats, we found that the mRNA expression levels of TLR9 and KLF4 were lower than those of the normal diet control group. In mature adipocytes, we found that KLF4 played an important anti-inflammatory role; moreover, PA can promote the development of inflammation by inhibiting KLF4 expression; TLR9 has a positive regulation function on KLF4 expression, but unrelated to PA. Conclusions TLR9/KLF4 is involved in regulating FFA-induced adipocyte inflammation.

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“…Wang et al conducted a study on omental adipocytes culture, rat models but also on humans [22]. In obese persons the mRNA expression levels of KLF4 were significantly lower than in the normalweight subjects and they significantly and negatively correlated with BMI, TG, and TNF-α [22]. These results are contradictory to our own ones, however they evaluated the mRNA expression of KLF4 not serum level and the study groups were totally different.…”

“…Comparison between KLF4 concentrations depending on BMI before and after treatment and controls KLF4 induced by obesity. Wang et al conducted a study on omental adipocytes culture, rat models but also on humans [22]. In obese persons the mRNA expression levels of KLF4 were significantly lower than in the normalweight subjects and they significantly and negatively correlated with BMI, TG, and TNF-α [22].…”

Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo‐osteogenic balance in bone marrow

“…Interestingly, the expression level of APN, specifically secreted by adipocytes, was significantly inhibited although the number of adipocytes was increased. We previously reported that APN expression was lower in adipose tissue of obese individuals, and palmitic acid inhibits APN expression in 3T3‐L1 adipocytes 36 . Reports in the literature have described how FAs, in addition to their role as bioenergetic sources, can also act as extracellular signaling molecules: FAs may affect different signaling pathways crucial to the biological functions of tumor cells, such as proliferation and invasion 37 .…”

Silencing of FSTL1 Alleviated LPS-Induced Inflammatory Damage and Oxidative Damage in Human Bronchial Epithelial Cells via BMP4/KLF4 Axis

“…In the kidney, KLF4 suppresses the proinflammatory differentiation of renal infiltrating macrophages and attenuates kidney injury and fibrosis by inhibiting myeloid cell generation of TNF-α [33]. Upregulation of KLF4 in mature adipocytes inhibited the expression of the inflammatory factors P65, TNF-α, IL-1β, and monocyte chemoattractant protein 1 and promoted the expression of the anti-inflammatory factor APN [34]. Studies have also shown that KLF4 may be involved in the pathogenesis of inflammatory bowel disease and esophageal epithelial inflammation by regulating the NF-κB signaling pathway [35,36].…”